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Single-cell and transcriptomic profiling reveal stemness-driven immune evasion in obstructive sleep apnea (OSA) associated lung cancer.
No full textObstructive sleep apnea (OSA) is characterized by recurrent intermittent hypoxia (IH) and has been increasingly associated with lung cancer incidence and mortality. However, how IH-related biological programs relate to immune remodeling, stemness-associated phenotypes, and therapeutic resistance in lung cancer remains incompletely understood. We integrated single-cell RNA sequencing data from IH-exposed murine lung tissues (GSE301350) with bulk transcriptomic datasets from TCGA-LUAD and GSE31210 to examine hypoxia-associated cellular and transcriptional patterns. Stemness was quantified using CytoTRACE and transcriptome-based stemness scoring, and its associations with immune infiltration, immune checkpoint expression, TIDE scores, predicted drug sensitivity, and immunotherapy response were evaluated. A stemness-based prognostic model was constructed using LASSO Cox regression and validated in independent cohorts. Single-cell analysis revealed marked immune remodeling under intermittent hypoxia (IH), including expansion of effector T cells, and monocytes/macrophages, populations alongside reduced B cells and dendritic cells. In human LUAD cohorts, stemness-high tumors were associated with mitochondrial and metabolic stress-related transcriptional programs, and increased expression of immune checkpoint genes (PD-1, PD-L1, CTLA4, LAG3). Elevated stemness scores correlated with higher TIDE scores, poorer overall survival, and reduced predicted responsiveness to immunotherapy. LASSO modeling identified a six-gene stemness signature (EIF5A, MELTF, SEMA3C, CPS1, TCN1, SELENOK), that consistently stratified patients into high- and low-risk groups across TCGA and GSE31210 cohorts. Multivariate Cox regression confirmed the risk score as an independent prognostic factor. Drug sensitivity analyses further suggested that stemness-high tumors may exhibit increased susceptibility to selected kinase inhibitors (Dasatinib, A-770041) and metabolic modulators (Phenformin, Salubrinal). OSA-associated IH is linked to stemness-associated transcriptional plasticity, immune suppression, and adverse clinical outcomes in lung cancer. The identified stemness-based gene signature provides a robust prognostic biomarker and highlights potential therapeutic vulnerabilities, supporting integrative strategies that combine stemness and immune -targeted approaches with immunotherapy in OSA-associated lung cancer
Career Plans Among Graduating US Emergency Medicine Residents.
No full textIMPORTANCE: The emergency medicine (EM) workforce is undergoing complex change, including a potential projected physician surplus, the volatile and evolving interests of medical students, and the continued high rates of burnout. Understanding the career intentions of graduating residents is critical to inform workforce planning.
OBJECTIVE: To examine the career plans, anticipated career durations, and key factors associated with the career decisions of graduating US EM residents.
DESIGN, SETTING, AND PARTICIPANTS: This cross-sectional survey study, which sampled graduating residents from all Accreditation Council for Graduate Medical Education-accredited categorical EM programs, was conducted after the 2023 American Board of Emergency Medicine In-Training Examination. Resident-level characteristics, including gender, race and ethnicity, educational debt, and burnout status, were examined. Data were obtained from June 20 to August 18, 2024, and analysis occurred from December 16, 2024, to August 12, 2025.
MAIN OUTCOMES AND MEASURES: Primary outcomes included immediate postresidency career plans, intended practice setting, anticipated years of clinical practice, and importance of 10 career decision factors.
RESULTS: Of 2782 eligible residents, 2711 (97.4%; 1394 men [51.4%]) responded to at least 1 survey item. Most respondents (1654 [61.0%]) reported educational debt exceeding 200 000 or more in debt (1376 [50.7%]) were significantly more likely to cite salary as a major factor (299 000: odds ratio [OR], 2.01 [95% CI, 1.39-2.89]; 399 000: OR, 2.31 [95% CI, 1.58-3.39]; ≥$400 000: OR, 1.58 [95% CI, 1.05-2.42]).
CONCLUSIONS AND RELEVANCE: In this survey study of graduating EM residents in 2023, most respondents planned to practice clinical EM for 2 decades primarily in community or hybrid settings, with a minority of residents interested in rural practice. Career decisions are overarching and encompass career factors; lifestyle, location, professional fulfillment, and salary were the strongest career factors. Burnout, educational debt, and demographic characteristics were associated with career decisions. These findings have implications for workforce modeling, retention strategies, and policies to support the EM workforce
Hip abduction with hip extension produces the largest obturator nerve displacement: a cadaveric investigation.
No full textBACKGROUND: The obturator nerve may be injured during surgery or trauma. Neurodynamic testing (NDT) is theorized to assist in obturator nerve injury identification, but the optimum hip position for NDT has not been biomechanically supported.
OBJECTIVES: This study evaluated the displacement and strain of the obturator nerve within the pelvis using three NDT positions of the hip (neutral, flexion, and extension) combined with hip abduction.
DESIGN: One-way repeated measures.
METHODS: Nine cadavers were selected by consecutive sampling, and metal markers were glued to the exposed intrapelvic obturator nerves
RESULTS: The obturator nerve displaced distally from the starting position during end-range hip abduction with the sagittal hip position in neutral (mean = 2.76 ± 2.46 mm;
CONCLUSION: Obturator nerve NDT using end-range hip abduction with the sagittal hip position in neutral or extension significantly displaces the nerve distally, suggesting these positions may be most useful when performing NDT of the obturator nerve
Neuroimaging features of cerebral air embolism: a matched case-control study.
No full textBACKGROUND AND PURPOSE: Cerebral air embolism (CAE) is a rare but treatable cause of ischemic stroke. Clinically, CAE may be difficult to distinguish from stroke due to more typical thromboembolic causes, but accurate diagnosis is critical to initiate appropriate treatment. We aimed to define the imaging features of CAE by comparing MRI from patients with confirmed CAE to those in cardioembolic stroke due to atrial fibrillation (AF).
MATERIALS AND METHODS: In a retrospective, matched case-control study, CAE cases from 2012-2023 were matched 1:2 by presenting NIHSS to control patients who had stroke due to AF and were not treated with thrombolytics or thrombectomy. MRIs were reviewed by a neuroradiologist blinded to group. The primary outcome was presence of pre-specified neuroimaging features on MRI.
RESULTS: Fourteen patients with stroke due to CAE (median age 61, 64% female, median NIHSS 12) and 28 controls with stroke due to AF (median age 81, 43% female, median NIHSS 12) were included. The predominant infarction topography in CAE patients was gyriform in 86%, punctate in 7%, and wedge-shaped in 7%, whereas in patients with stroke due to AF the predominant infarction topography was wedge-shaped in 71%, punctate in 18%, and gyriform in 11% (p\u3c 0.001). CAE patients more often presented with multiple (93% versus 50%, p=0.007) and bilateral infarctions (79% versus 43%, p=0.05). Cortical borderzone involvement was more frequent in patients with CAE compared to those with AF (86% versus 25%, p\u3c 0.001). The presence of both predominantly gyriform infarction topography and cortical borderzone involvement had a 76.6% sensitivity and 96.4% specificity for CAE.
CONCLUSIONS: CAE cause characteristic gyriform infarction patterns on MRI that are distinct from typical cardioembolic stroke. In addition, cortical borderzone predilection and multifocal infarctions were substantially more frequent in CAE. This constellation of findings, in the appropriate clinical context, should strongly suggest CAE as the mechanism of neurologic injury, and may facilitate timely identification of this uncommon but critical diagnosis
Sex-Related Differences in Outcomes of Left Atrial Appendage Occlusion Device Placement.
No full textBACKGROUND: Atrial fibrillation (AF) is associated with profound morbidity and mortality, including a fivefold increase in stroke risk. Left atrial appendage occlusion (LAAO) devices have emerged as an alternative approach to anticoagulation in patients with elevated bleeding risk and/or have contraindications to anticoagulation. However, females have been underrepresented in PROTECT & PREVAIL landmark trials supporting LAAO use. We aim to compare gender differences in outcomes of LAAO occlusive devices.
METHODS: The national readmission database (2016-2020) was utilized to identify hospitalizations for LAAO placement. Cohorts were stratified by gender as males and females. A propensity score matching (PSM) model matched both cohorts. Pearson\u27s x2 test was applied to the matched cohorts to compare outcomes.
RESULTS: Among 89,552 hospitalizations for LAAO placement, 41.3% of procedures were performed in females. Females were found to have a lower prevalence of co-morbidities such as diabetes, hypertension, hyperlipidemia and CKD [p \u3c 0.001]. After propensity matching (N = 20,627), females had higher adverse events, including mortality (0.23% vs. 0.15%, p: 0.041), sudden cardiac arrest (1.77% vs. 1.37%, p: 0.001), pericardial complications (1.46% vs. 0.86%, p \u3c 0.001), cardiac tamponade (0.94% vs. 0.54%, p \u3c 0.001), post-procedural bleeding (0.69% vs. 0.53%, p: 0.032) & net adverse events (4.73% vs. 4.24%, p \u3c 0.001). At six-month follow-up post-procedure, females had higher readmission rates at 30 days (9.42% vs. 8.07%, p \u3c 0.001), 90-day and 180-day intervals (p \u3c 0.001).
CONCLUSION: In patients with hospitalizations for LAAO device placement, we observed a higher risk of net adverse events and mortality in females following the procedure compared to males. Prospective trials are warranted to identify and stratify the at-risk population with extensive preprocedural evaluation and determine ways to mitigate the sex-related disparities in clinical outcomes following the LAAO procedure
Short- and Long-term Metabolic Exposure Data as Predicators of Coronary Microvascular Dysfunction in a Positron Emission Tomography Myocardial Perfusion Imaging (PET-MPI) Cohort with Near Concurrent Angiography.
No full textBackgroundCoronary microvascular disease (CMD) is defined by impaired myocardial stress flow reactivity and is associated with worse cardiovascular outcomes. Studying CMD is complicated by the overlap of its risk factors and patient-important cardiovascular sequelae with those of epicardial atherosclerotic disease. Published studies have not yet used longitudinal data to investigate the time dependencies of dynamic processes like obesity in their effects on microvascular health.Methods and ResultsIn a mixed-sex cohort of 85 patients for whom epicardial obstruction was angiographically excluded, a multivariate model was developed to measure strengths of association between repeated-measurement metabolic data and microvascular stress flow reactivity as assessed by position emission tomography myocardial perfusion imaging (PET-MPI). Body mass index and the diagnosis of insulin-dependent diabetes mellitus were associated with CMD on clinically meaningful scales when analyzing all metabolic data collected in the year prior to stress PET-MPI (β [95%CI]: -0.019 [-0.033,-0.0051]
Describing genetic variants in neurological vascular malformations: Clinical features & treatment implications
No full textOptimal Timing of Cranioplasty After Craniectomy: A Systematic Review and Meta-Analysis.
No full textBACKGROUND AND OBJECTIVES: The optimal timing of cranioplasty (CP) after craniectomy remains uncertain. We aimed to evaluate and compare functional outcomes and complication rates associated with early and late CP after craniectomy.
METHODS: We systematically searched PubMed, Scopus, and Web of Science through June 2025. Fifty-five studies (n = 8602 patients) met inclusion criteria, comparing at least 2 distinct CP timing categories. Functional outcomes included Barthel Index (BI), functional independence measure, and modified motor assessment and enhancement scale. Patients were categorized as having undergone ultra-early CP (30-45 days), intermediate CP (45-70 days), early CP (80-100 days), or delayed CP (120-180 days).
RESULTS: Early CP significantly improved functional outcomes in BI absolute scores, BI gain scores, absolute functional independence measure scores, and absolute modified motor assessment and enhancement scale scores compared with delayed CP. Ultra-early CP demonstrated the greatest benefit in absolute BI scores and significantly reduced bone flap resorption risk. No significant differences were found in rates of complications. Implant material (autologous vs prosthetic) and traumatic etiology did not significantly affect these outcomes.
CONCLUSION: Earlier CP after craniectomy-particularly within 100 days-was associated with improved functional recovery without a significant increase in complications. Although bone flap resorption appeared lower with ultra-early timing, other adverse events such as infection, hydrocephalus, and hematoma did not vary meaningfully across timing windows. These findings suggest that, in carefully selected patients, earlier reconstruction may offer neurological benefits. Because timing was not randomized and may reflect clinical stability and treatment selection, these findings reflect associations and do not establish causality. Further studies are needed
Prediabetes and chronic kidney disease: a comprehensive review of association and clinical implications.
No full textPrediabetes affects nearly one-third of adults in the United States and is increasingly recognized as a contributor to early chronic kidney disease (CKD). This review summarizes current evidence linking prediabetes with early kidney changes, including albuminuria, glomerular hyperfiltration, and mild renal impairment, as well as its association with increased cardiovascular risk. Large observational cohorts, such as the Chronic Renal Insufficiency Cohort, suggest an association between prediabetes and progression of proteinuria, although its independent contribution to advanced CKD remains variable. We review proposed mechanisms, including insulin resistance, low-grade hyperglycemia, altered tubulo-glomerular feedback mediated by sodium-glucose cotransporter 2 activity, inflammation, and endothelial dysfunction. Variability in diagnostic thresholds across major guidelines complicates risk stratification. Emerging biomarkers may facilitate earlier detection but require further validation. Early identification and guideline-directed lifestyle and pharmacological interventions may help mitigate CKD progression and related cardiovascular outcomes. These insights inform population-level screening, prevention, and decision-making